Thymidylate synthase expression in metastatic colorectal cancer: correlation with the clinical response to leucovorin- modulated 5-fluorouracil

Abstract EN

Purpose : the aim of the present study is to determine whether the level thymidylate synthase (TS) expression predicts the clinical response to fluorouracil (FU)-based chemotherapy in patients with recurrent or metastatic col-orectal cancer.

Patients and methods : TS levels were measured on immunohistochemically specimens of colorectal cancer metastases or recurrences from 48 patients (30 males and 18 females; median age, 49 years) treated with 5FU (420 mg / m2 i.v.

days 1-5) and LV (20 mg / m2 i.v.

days 1-5) ; cycles were repeated every 28 days.

These measurements were correlated with patient characteristics and clinical outcome.

Results : A significant correlation was found between TS expression and all the parameters of clinical outcome analyzed.

In patients whose tumors had low (n = 27) and high (n = 21) TS levels, the overall response rates were 66.7 % and 23.8 %, respectively (p = 0.003).

The percentage of tumor shrinkage after chemotherapy was linearly related to TS immunoreactivity (r = 0.56, p = 0.00004) and its mean values were 65 % and 14 % with low and high TS levels, respectively (p = 0.0001).

By logistic regression analysis, low TS expression was the single best predictor of response to 5FU based-chemotherapy (relative probability, 5.0).

In patients with low and high TS expression, the median time to progression was 9.6 months vs 6.2 months (p = 0.005) and the median survival time 18.4 months vs 15.4 months (p = 0.02), respectively.

Two- and 3-year survival rates were 41 % vs 15 % and 19 % vs 0 % (p = 0.02), respectively.

Conclusion : our results demonstrate the ability of TS protein expression to predict response to 5FUra.

This could have a significant impact on the choice of drugs in treatment of advanced colorectal cancer and may change the therapeutic approach from a general to an individual treatment strategy.